PROJECT SUMMARY The clinical trial of Towards a Revolution in COPD Health (TORCH) has previously compared salmeterol (long acting beta-2 selective adrenergic agonist [LABA] bronchodilator) plus fluticasone (steroid), administered as a single inhaler, with placebo over a 3-year period in 6,112 participants with a mean age of 65 years and moderate-to-severe chronic obstructive pulmonary disease (COPD). The primary outcome was all-cause mortality, but the treatment effect did not meet the predetermined level of statistical significance. We note, however, that the TORCH trial established COPD and its severity based on spirometric criteria from the Global initiative for chronic Obstructive Lung Disease (GOLD). The latter criteria increasingly misidentify COPD in aging populations, starting at ages >45-50 years. As an alternative approach, spirometric Z-scores that are calculated from reference equations by the Global Lung Initiative (GLI) rigorously account for age- related changes in lung function and are associated with important health outcomes. Hence, using existing high-quality data, we propose to reclassify lung function in the TORCH trial by using (GLI-calculated) spirometric Z-scores. We will then evaluate the consequence of the misidentification of moderate-to-severe COPD, as an additional covariate, on the primary outcome of all-cause mortality, as well as on the secondary outcomes of exacerbations, health status, lung function, and adverse events, comparing salmeterol plus fluticasone to placebo over a 3-year period (study population and randomization is maintained). We will also redefine the TORCH study population as including only those participants with spirometric Z-score defined moderate-to-severe COPD. Although this latter approach loses the benefits of randomization, it will evaluate the associations of salmeterol plus fluticasone with the same outcomes, relative to placebo, but with results specific to spirometric Z-score defined moderate-to-severe COPD. Lastly, to further assess bronchodilator therapy, we propose to additionally evaluate tiotropium, a long acting muscarinic antagonist [LAMA] bronchodilator, using existing data from the UPLIFT trial (N=5993, mean age 65 years, GOLD defined moderate-to-severe COPD, 4-year study) and including similar analyses as above.